PT - JOURNAL ARTICLE AU - Chang, Julie AU - Saraswathibhatla, Aashrith AU - Song, Zhaoqiang AU - Varma, Sushama AU - Sanchez, Colline AU - Srivastava, Sucheta AU - Liu, Katherine AU - Bassik, Michael C. AU - Marinkovich, M. Peter AU - Hodgson, Louis AU - Shenoy, Vivek AU - West, Robert B. AU - Chaudhuri, Ovijit TI - Collective invasion of the basement membrane in breast cancer driven by forces from cell volume expansion and local contractility AID - 10.1101/2022.07.28.501930 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.07.28.501930 4099 - http://biorxiv.org/content/early/2022/07/31/2022.07.28.501930.short 4100 - http://biorxiv.org/content/early/2022/07/31/2022.07.28.501930.full AB - Breast cancer becomes invasive when carcinoma cells collectively invade through the basement membrane (BM), a nanoporous layer of matrix that physically separates the primary tumor from the stroma, in a first step towards metastasis. Single cells can invade through nanoporous three-dimensional (3D) matrices via protease-mediated degradation or, when the matrix exhibits sufficient mechanical plasticity, force-mediated widening of pores. However, how cells invade collectively through physiological BM layers in cancer remains unclear. Here, we developed a 3D in vitro model of collective invasion of the BM during breast cancer. We show that cells utilize both proteases and forces to breach the BM. Forces are generated from a combination of global cell volume expansion that stretch the BM with local contractile forces that act in the plane of the BM to breach it, allowing invasion. These results uncover a mechanism by which cells collectively interact to overcome a critical barrier to metastasis.Competing Interest StatementThe authors have declared no competing interest.